a single center study of donafenib combined with pd-1 + tace in the first-line treatment of ahcc

Conditions: Donafenib

Summary: this study is expected to recruit 30 patients with unresectable hcc who will be treated with donafenib combined with pd-1 + tace. during the study period, the tumor efficacy and resectability will be evaluated by imaging examination every 6 weeks. patients with successful transformation can choose hepatectomy or observation. during the study, safety evaluation and effectiveness evaluation will be carried out.


Eligibility criteria:
inclusion criteria: 1. patients voluntarily enter the study and sign informed consent form (icf); 2. age ≥ 18 years and ≤ 75 years, and there is no limit on the gender; 3. clinically or histologically diagnosed as unresectable hcc; 4. there is at least one measurable lesions that meet the mrecist standard; 5. child-pugh classification a or b (score≤7); 6. ecog : 0 \~ 1 ; 7. the number of intrahepatic tumors ≤ 10 and the maximum tumor diameter ≤ 10cm; 8. previous tace treatment ≤ 1 time; 9. life expectancy ≥ 3 months; 10. for patients with hbv infection, if hbv-dna is≥10\^4copies/ml within 14 days before enrollment, they should take antiviral treatment first, reduce 1 log or reduce to \<10\^4copies/ml before entering the study, and continue antiviral treatment and monitor liver function and serum hbv-dna levels; 11. baseline blood routine and biochemical indexes meet the following criteria within 14 days before treatment: blood routine examination criteria must be met: (no blood transfusion within 14 days) 1. hb≥90g/l； 2. anc≥1.5×10\^9/l； 3. plt≥70×10\^9/l. biochemical tests are subject to the following criteria: 1. bil \<1.25xuln ； 2. alt and ast\<5xuln； 3. serum creatinine. less than 1.5 times the upper limit of normal value, endogenous creatinine clearance\>50ml/min ( cockcroft-gault formula)； 4. albumin≥28g/l； 5. electrolytes (phosphorus, calcium, magnesium, potassium) ≥ lln; 6. urine protein \<2+ or 24-hour urine protein quantitative detection ≤1.0 g/l. blood coagulation indexes are subject to the following criteria: 1. prothrombin time (pt) and international normalized ratio (inr) ≤1.5 × uln; 2. activated partial thromboplastin time（aptt）≤1.5 × uln. 12. the serum pregnancy test results of female patients with fertility (referring to premenopausal or non surgical sterilization) must be negative within 14 days before enrollment. exclusion criteria: 1. pathologically confirmed hepatocellular carcinoma intrahepatic cholangiocarcinoma (hcc-icc) mixed or fibrolamellar hepatocellular carcinoma; 2. the presence of a tumor thrombus in the main portal vein, biliary tract tumor thrombus, inferior vena cava tumor thrombus, or extrahepatic metastasis; 3. hepatocellular carcinoma recurrence within 2 years after radical resection or ablation; 4. history of malignancy other than hcc within 5 years; 5. esophageal and/or gastric varices bleeding within 4 weeks prior to initiation of study treatment; 6. presence of uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion; 7. patients who received liver transplant surgery, prior systemic therapy (chemotherapy, targeted therapy or immunotherapy) or palliative local treatment ≥2 times for hcc； 8. history of organ and cell transplantation； 9. tace contraindications identified by the investigator; 10. active severe infection; 11. autoimmune disease or immune deficiency; 12. severe organ (heart, kidney) dysfunction; 13. pregnant or breastfeeding women, and women or men with fertility who are unwilling or unable to take effective contraceptive measures; 14. unable to follow the research protocol for treatment or scheduled follow-up; any other researcher who thinks they cannot be included.

Keywords: donafenib hepatocellular carcinoma